Effects of centrally-acting glutamatergic modulators on cardiovascular responses to stress in humans

Sympathetic overactivity is a common feature of certain cardiovascular diseases. An acute activation of the sympathetic nervous system can provoke angina pectoris attacks through the increase of myocardial oxygen demand, frequently associated to coronary arterial constriction. It can also promote cardiac arrhythmias leading, in some cases, to cardiac sudden death. The aim of the present study was to evaluate the cardiovascular effects of a single oral dose of baclofen or ifenprodil (two drugs modulating central glutamatergic relays) at rest and during three laboratory stressors (a cold pressor test, a mental arithmetic stress test and an exercise test on a cycloergometer), in human healthy volunteers. Ifenprodil increased resting heart rate and did not reduce the cardiovascular response to any test. In contrast, baclofen reduced the tachycardic response to mental stress test and so limited the increase of myocardial oxygen demand during the test. Nevertheless, this drug was not able to affect the cardiovascular response to exercise. Finally, we have shown in this study that baclofen exhibits a profile of a central sympathomodulator without cardiodepression. Its activity towards mental stress induced cardiovascular responses leads us to proposing this compound for testing after a chronic treatment, in patients with silent myocardial ischemia and mental stress test induced ischemia.